This laboratory is investigating the chemical nature of compounds that regulate reproduction in mammals via chemosensory mechanisms, with an emphasis on pheromones that are detected by non-olfactory nasal chemoreceptors. During the proposed grant period the goal is to complete the chemical characterization of female pheromones in hamsters and mice that stimulate elevated sex hormone levels and copulatory behavior in males. Immediate aims include (1) the determination of whether a low molecular weight ligand is necessary for the behavioral activity of aphrodisin, the hamster vaginal discharge protein that stimulates male copulatory behavior, and (2) the completion of a parallel effort to identify low molecular weight compounds in female mouse urine that elicit rapid gonadotropin surges in males. Results from these two investigations will be used to guide the identification of female hamster pheromones that similarly elicit male sex hormone surges. Characterization of these pheromones in hamsters and mice will enable us to compare the structures of two vomeronasally detected pheromones and provide us with a test of our hypothesis that reproductive pheromones detected by specialized nasal chemoreceptors are also specialized and therefore may be structurally similar in various mammalian species. These results could enable us to make fruitful predictions about the chemical nature of pheromones in higher mammalian species. Regardless of whether this hypothesis proves to be valid however, identification of these compounds will enable us to provide our collaborators with probes useful for study of the mechanisms of chemosensory regulation of reproduction. Furthermore, these compounds could prove to be useful pharmacological agents that have specific effects on hormone levels, sexual behavior, aggression, and fertility.